中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2015年
4期
272-275
,共4页
苏珊%陈向东%汪辉%高聪%吕瑞雪
囌珊%陳嚮東%汪輝%高聰%呂瑞雪
소산%진향동%왕휘%고총%려서설
泰比培南酯%肺炎克雷伯菌%肺部感染模型%药代动力学/药效学
泰比培南酯%肺炎剋雷伯菌%肺部感染模型%藥代動力學/藥效學
태비배남지%폐염극뢰백균%폐부감염모형%약대동역학/약효학
tebipenem pivoxil%Klebsiella pneumoniae%lung infection model%PK/PD
目的:通过泰比培南酯对小鼠肺炎克雷伯菌感染模型药代动力学/药效学( PK/PD)研究,预测最佳PK/PD参数。方法取临床肺炎克雷伯菌1株,用琼脂二倍稀释法检测泰比培南的最低抑菌浓度( MIC);构建小鼠的肺炎克雷伯菌肺部感染模型,给予3种剂量(50,15,3 mg? kg-1)的泰比培南酯,观察给药24 h后肺组织感染量变化,并用高效液相色谱( HPLC )法检测血药浓度。结果体外测得MIC为0.03μg? mL-1;在小鼠的肺炎克雷伯菌肺部感染模型中,3种剂量均对感染有治疗作用,PK/PD参数AUC/MIC、Cmax/MIC及T>MIC的相关系数(r)分别为0.78,0.76和0.46。结论 AUC/MIC和Cmax/MIC参数是反映泰比培南酯对小鼠的肺炎克雷伯菌肺部感染疗效的主要PK/PD参数。
目的:通過泰比培南酯對小鼠肺炎剋雷伯菌感染模型藥代動力學/藥效學( PK/PD)研究,預測最佳PK/PD參數。方法取臨床肺炎剋雷伯菌1株,用瓊脂二倍稀釋法檢測泰比培南的最低抑菌濃度( MIC);構建小鼠的肺炎剋雷伯菌肺部感染模型,給予3種劑量(50,15,3 mg? kg-1)的泰比培南酯,觀察給藥24 h後肺組織感染量變化,併用高效液相色譜( HPLC )法檢測血藥濃度。結果體外測得MIC為0.03μg? mL-1;在小鼠的肺炎剋雷伯菌肺部感染模型中,3種劑量均對感染有治療作用,PK/PD參數AUC/MIC、Cmax/MIC及T>MIC的相關繫數(r)分彆為0.78,0.76和0.46。結論 AUC/MIC和Cmax/MIC參數是反映泰比培南酯對小鼠的肺炎剋雷伯菌肺部感染療效的主要PK/PD參數。
목적:통과태비배남지대소서폐염극뢰백균감염모형약대동역학/약효학( PK/PD)연구,예측최가PK/PD삼수。방법취림상폐염극뢰백균1주,용경지이배희석법검측태비배남적최저억균농도( MIC);구건소서적폐염극뢰백균폐부감염모형,급여3충제량(50,15,3 mg? kg-1)적태비배남지,관찰급약24 h후폐조직감염량변화,병용고효액상색보( HPLC )법검측혈약농도。결과체외측득MIC위0.03μg? mL-1;재소서적폐염극뢰백균폐부감염모형중,3충제량균대감염유치료작용,PK/PD삼수AUC/MIC、Cmax/MIC급T>MIC적상관계수(r)분별위0.78,0.76화0.46。결론 AUC/MIC화Cmax/MIC삼수시반영태비배남지대소서적폐염극뢰백균폐부감염료효적주요PK/PD삼수。
Objective To elucidate the pharmacokinetic/pharmacody-namic ( PK/PD ) parameters that predict tebipenem pivoxil efficacy against Klebsiella pneumoniae in murine lung infection model. Methods The minimal inhibitory concentration ( MIC ) of tebipenem pivoxil against Klebsiella pneumoniae was determined by standard two-fold agar dilution method.Three doses of 50, 15 and 3mg? kg-1 were given to lung infection models, respectively.The bacterial burden in lung was measured 24 hours after the initiation of treatment and the concentra-tion in plasma was determined by high performance liquid chromatogra-phy ( HPLC) .Results The MIC value was 0.03 μg? mL-1 .Three doses all showed effects on murine lung infection model.Three PK/PD parameters correlated with efficacy of tebipenem pivoxil were AUC/MIC ( r =0.78 ) , Cmax/MIC ( r =0.76 ) , and T >MIC ( r =0.46 ) . Conclusion PK/PD study indicates AUC/MIC and Cmax/MIC are PK/PD parameters, well correlated with the efficacy of tebipenem pivoxil against Klebsiella pneumoniae in murine lung infection model.